Hot Flushes, Night Sweats
Conditions
Keywords
hot flushes/hot flashes, night sweats, sleep problems, negative mood, anxiety, perimenopause, progesterone, vasomotor symptoms, depression, women's perceived change, perimenopause interference questionnaire
Brief summary
The purpose of this study is to test whether a oral micronized progesterone reduces the Vasomotor Symptom Score comprised of the number and severity of hot flushes and night sweats in perimenopausal women. Oral micronized progesterone is molecularly identical to human progesterone, a steroid hormone. It is sold by prescription for use to prevent endometrial cancer in women taking estrogen in menopause. This research study will test whether progesterone reduces perimenopausal hot flushes and night sweats. It will also test whether progesterone improves sleep disturbances and anxiety.
Detailed description
This is a randomized, double-blind placebo-controlled trial of oral micronized progesterone (300 mg daily at bedtime) for perimenopausal women living anywhere in Canada. Using the self-reported maximum menstrual cycle length in the previous year, women will be stratified as in Early Perimenopause (\<60 days) or Late Perimenopause (\>=60 days). The design includes a 28-day baseline run-in followed by 12 weeks of randomized therapy.
Interventions
300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks
DRUGplacebo
placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 58 Years
Healthy volunteers
No
Inclusion criteria
1. Between 35-58 years of age 2. At least 4 vasomotor symptoms (VMS) per day, on average, for at least 2/4 weeks or at least 56 over a four-week period. In addition, women should report having VMS of moderate or severe rather than mild intensity. Women reporting fewer VMS than this, but who report night sweats that awaken them from sleep on two or more nights per week will also be included. 3. Perimenopausal status either based on irregularity of menstrual periods, or by onset of new perimenopausal symptoms in women with regular periods. 4. At least one menstrual period within 12 months of study enrollment 5. Ability and willingness to complete the Daily Perimenopause Hot Flush Calendar recording instrument. 6. Ability to understand, speak, read and write English. 7. Women who are at high risk for breast cancer (ie first degree relative with breast cancer, known/suspected history of breast cancer) will be required to have a normal mammogram and clinical breast examination within 12 months of study enrollment.
Exclusion criteria
1. VMS without perimenopausal etiology. 2. Women who have had a hysterectomy and/or ovariectomy. 3. Peanut allergy (because peanut oil is used in the progesterone formulation.) 4. Current or recent (within the last 6-mos.) use of hormonal therapies (estrogen, progesterone, hormonal contraceptives, hormonal fertility treatments), or plans to initiate use during the study period. Two exceptions: women using progestin-releasing intrauterine device (IUD) will not be excluded as it is felt that level of hormone released will not have an effect on VMS and women taking very low-dose transdermal progesterone therapies who have VMS and meet inclusion criteria will be considered on a case-by-case basis. If enrolled, women with these exclusion exceptions will be required to continue and document use of these therapies throughout the entire trial. 5. Planned pregnancy or fertility treatment during the study period. 6. Women who are breastfeeding. 7. Participants with a score greater or equal to 15 on the Personal Health Questionnaire (PHQ-9) will be assessed on a case-by-case basis. Women assessed as needing further investigation and/or treatment for depression will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks | 12 weeks | Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. |
| Frequency of VMS | 12 weeks | Frequency (count) of hot flushes/hot flashes and night sweats per day from prospective daily calendar records. Outcome is the average daily VMS Frequency (day + night) during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. |
| Severity of VMS | 12 weeks | Severity (0-4, 0=no intensity, 4=extreme intensity) of hot flushes/hot flashes and night sweats per day from prospective daily calendar records. Daily summary score is the maximum of daytime and nighttime severity. Outcome is the average daily severity during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. |
| VMS Score by Early Perimenopause | 12 weeks | subgroup analysis of VMS Score by Early Perimenopause (no skipped period or \<60 day cycle length). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity). |
| VMS Score by Late Perimenopause | 12 weeks | subgroup analysis of VMS Score by Late Perimenopause (those with skipped or ≥60 day cycle lengths). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity). |
| Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score | 12 weeks | VMS Score for those with more frequent (≥7 per day and moderate to severe episodes of intensity 2-4) at baseline. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause | 12 weeks | Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) at 12 weeks in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference) |
| Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause | 12 weeks | Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) at 12 weeks in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference) |
| Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women | 12 weeks | Final perceptions of interference of perimenopausal body changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference) |
| Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women | 12 weeks | Final perceptions of interference of perimenopausal mood changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference) |
| Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire and by subgroup for Early Perimenopause. Scale Name: Perceived Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. |
| Women's Perceived Changes in Night Sweats in Early Perimenopause | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire and by subgroup for Early Perimenopause. Scale Name: Perceived Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. |
| Sleep Problems | 12 weeks | Daily average rating of sleep problems (0-4) from prospective daily calendar records. Outcome is the average daily rating during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Scale name: Sleep Problems (4=Worst, 0=None) |
| Women's Perceived Changes in Night Sweats in Late Perimenopause | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire and by subgroup for Late Perimenopause. Scale Name: Perceived Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. |
| Depression Related to Progesterone Therapy in Whole Population | 12 weeks | Final PHQ9 (Personal Health Questionnaire 9) Score for Depression related to progesterone therapy in perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo. Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression) |
| Depression Related to Progesterone Therapy in Early Perimenopause | 12 weeks | Final PHQ9 Score for Depression related to progesterone therapy in Early Perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo. Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression) |
| Depression Related to Progesterone Therapy in Late Perimenopause | 12 weeks | Final PHQ9 Score for Depression related to progesterone therapy in Late Perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo. Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression) |
| Percentage of Women With Perceived Changes in Menstrual Flow | 12 weeks | Menstrual flow related to progesterone therapy in perimenopause was assessed based on Women's Perceived Changes Questionnaire of changes in the experience of menstrual flow/vaginal bleeding from the Final Questionnaire. |
| Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire and by subgroup for Late Perimenopause. Scale Name: Perceived Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. |
| Anxiety | 12 weeks | Daily average rating of anxiety (0-4) from prospective daily calendar records. Outcome is the average daily rating during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Scale name: Anxiety (4=Worst, 0=None) |
| Women's Perceived Changes in Daytime Hot Flushes for Whole Population | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire. Scale Name: Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks). No calculation is needed. |
| Women's Perceived Changes in Night Sweats for Whole Population | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire. Scale Name: Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks). No calculation is needed. |
| Women's Perceived Changes in Quality of Sleep for Whole Population | 12 weeks | Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in the quality of sleep over the three months of the trial as assessed by the Final Questionnaire based on their random assignment to the progesterone or placebo arms of this RCT (Randomized Controlled Trial) and by Early/Late perimenopause. Scale Name: Quality of Sleep Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks). No calculation is needed. |
| Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women | 12 weeks | Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR PIQ - Centre for Menstrual Cycle and Ovulation Research Perimenopause Interference Questionnaire) at 12 weeks in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference) |
Countries
Canada
Participant flow
Pre-assignment details
Enrollment required meeting eligibility criteria by screening questionnaire but also required eligible hot flushes and night sweats on a 28-day Calendar. The difference between the listed enrolled and those who were randomized represents this fact.
Participants by arm
| Arm | Count |
|---|---|
| Oral Micronized Progesterone Oral micronized progesterone is Prometrium 300 mg at bedtime daily
Oral micronized progesterone: 300 mg as 3-100 mg capsules taken orally at bedtime daily for 12 weeks | 93 |
| Placebo Comparator Placebo
placebo: placebo comparator, taken as 3 round capsules at bedtime daily for 12 weeks | 96 |
| Total | 189 |
Baseline characteristics
| Characteristic | Placebo Comparator | Total | Oral Micronized Progesterone |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 96 Participants | 189 Participants | 93 Participants |
| Age, Continuous | 50.4 years STANDARD_DEVIATION 4.2 | 49.9 years STANDARD_DEVIATION 4.6 | 49.4 years STANDARD_DEVIATION 5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 11 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) White | 82 Participants | 165 Participants | 83 Participants |
| Region of Enrollment Canada | 96 participants | 189 participants | 93 participants |
| Sex: Female, Male Female | 96 Participants | 189 Participants | 93 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 96 |
| other Total, other adverse events | 22 / 93 | 8 / 96 |
| serious Total, serious adverse events | 0 / 93 | 0 / 96 |
Outcome results
Primary
Frequency of VMS
Frequency (count) of hot flushes/hot flashes and night sweats per day from prospective daily calendar records. Outcome is the average daily VMS Frequency (day + night) during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Frequency of VMS | 2.4 episodes per day | Standard Deviation 2.7 |
| Placebo Comparator | Frequency of VMS | 3.0 episodes per day | Standard Deviation 3.7 |
Primary
Severity of VMS
Severity (0-4, 0=no intensity, 4=extreme intensity) of hot flushes/hot flashes and night sweats per day from prospective daily calendar records. Daily summary score is the maximum of daytime and nighttime severity. Outcome is the average daily severity during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Severity of VMS | 1.4 Units on a Scale of 0-4 | Standard Deviation 1 |
| Placebo Comparator | Severity of VMS | 1.5 Units on a Scale of 0-4 | Standard Deviation 1 |
Primary
Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score
VMS Score for those with more frequent (≥7 per day and moderate to severe episodes of intensity 2-4) at baseline. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score | 11.8 Units of Vasomotor Symptom Score | Standard Deviation 9 |
| Placebo Comparator | Subgroup Analysis for Those With Frequent and Severe VMS - VMS Score | 15.1 Units of Vasomotor Symptom Score | Standard Deviation 17.1 |
Primary
Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks
Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate.
Time frame: 12 weeks
Population: Intent to Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks | 5.5 Units of Vasomotor Symptom Score | Standard Deviation 8.2 |
| Placebo Comparator | Vasomotor Symptoms (VMS)/ VMS Score - at 12 Weeks | 7.1 Units of Vasomotor Symptom Score | Standard Deviation 10.4 |
Primary
VMS Score by Early Perimenopause
subgroup analysis of VMS Score by Early Perimenopause (no skipped period or \<60 day cycle length). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | VMS Score by Early Perimenopause | 4.4 Units of Vasomotor Symptom Score | Standard Deviation 7.4 |
| Placebo Comparator | VMS Score by Early Perimenopause | 3.9 Units of Vasomotor Symptom Score | Standard Deviation 4 |
Primary
VMS Score by Late Perimenopause
subgroup analysis of VMS Score by Late Perimenopause (those with skipped or ≥60 day cycle lengths). Outcome is the average daily VMS Score during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Participants will complete a daily calendar (Daily Perimenopause Hot Flush Calendar) to record frequency (actual number) and severity (quantified by ordinal scale ie 0=none to 4=extreme) of hot flushes and night sweats. The VMS Score will be calculated as follows: Daily VMS Score = (# night sweats) x (severity) + (#hot flushes) x (severity).
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | VMS Score by Late Perimenopause | 5.9 Units of Vasomotor Symptom Score | Standard Deviation 8.5 |
| Placebo Comparator | VMS Score by Late Perimenopause | 8.8 Units of Vasomotor Symptom Score | Standard Deviation 12.3 |
Secondary
Anxiety
Daily average rating of anxiety (0-4) from prospective daily calendar records. Outcome is the average daily rating during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Scale name: Anxiety (4=Worst, 0=None)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Anxiety | 0.5 Units on a ordinal Scale | Standard Deviation 0.6 |
| Placebo Comparator | Anxiety | 0.6 Units on a ordinal Scale | Standard Deviation 0.8 |
Secondary
Depression Related to Progesterone Therapy in Early Perimenopause
Final PHQ9 Score for Depression related to progesterone therapy in Early Perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo. Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Depression Related to Progesterone Therapy in Early Perimenopause | 6.0 PHQ9 Scale: 0-27 | Standard Deviation 4.6 |
| Placebo Comparator | Depression Related to Progesterone Therapy in Early Perimenopause | 5.4 PHQ9 Scale: 0-27 | Standard Deviation 3.6 |
Secondary
Depression Related to Progesterone Therapy in Late Perimenopause
Final PHQ9 Score for Depression related to progesterone therapy in Late Perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo. Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Depression Related to Progesterone Therapy in Late Perimenopause | 4.4 PHQ9 Scale: 0-27 | Standard Deviation 4.3 |
| Placebo Comparator | Depression Related to Progesterone Therapy in Late Perimenopause | 5.4 PHQ9 Scale: 0-27 | Standard Deviation 4.6 |
Secondary
Depression Related to Progesterone Therapy in Whole Population
Final PHQ9 (Personal Health Questionnaire 9) Score for Depression related to progesterone therapy in perimenopause will be assessed based on the Personal Health Questionnaire-9 (PHQ-9) score changes within-woman from baseline to the end-of-trial on progesterone compared with placebo. Scale Name: PHQ9 Scale (0 = No Depression; 27 = Severe Depression)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Depression Related to Progesterone Therapy in Whole Population | 4.8 PHQ9 Scale: 0-27 | Standard Deviation 4.4 |
| Placebo Comparator | Depression Related to Progesterone Therapy in Whole Population | 5.4 PHQ9 Scale: 0-27 | Standard Deviation 4.3 |
Secondary
Percentage of Women With Perceived Changes in Menstrual Flow
Menstrual flow related to progesterone therapy in perimenopause was assessed based on Women's Perceived Changes Questionnaire of changes in the experience of menstrual flow/vaginal bleeding from the Final Questionnaire.
Time frame: 12 weeks
Population: The discrepancy in the Number of Participants analyzed is due to missing data on the Final Questionnaire.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Micronized Progesterone | Percentage of Women With Perceived Changes in Menstrual Flow | 65 Participants |
| Placebo Comparator | Percentage of Women With Perceived Changes in Menstrual Flow | 74 Participants |
Secondary
Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women
Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR PIQ - Centre for Menstrual Cycle and Ovulation Research Perimenopause Interference Questionnaire) at 12 weeks in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women | 22.6 Visual Analogue scale 0-100 mm | Standard Deviation 18.3 |
| Placebo Comparator | Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women | 28.2 Visual Analogue scale 0-100 mm | Standard Deviation 21.7 |
Secondary
Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause
Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) at 12 weeks in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause | 25.7 Visual Analogue scale 0-100 mm | Standard Deviation 20.2 |
| Placebo Comparator | Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Early Perimenopause | 33.0 Visual Analogue scale 0-100 mm | Standard Deviation 22.7 |
Secondary
Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause
Final perceptions of interference of overall perimenopausal changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) at 12 weeks in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause | 21.3 Visual Analogue scale 0-100 mm | Standard Deviation 17.5 |
| Placebo Comparator | Perception of Interference of Overall Perimenopausal Changes With Usual Activities in Women - Late Perimenopause | 25.6 Visual Analogue scale 0-100 mm | Standard Deviation 20.9 |
Secondary
Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women
Final perceptions of interference of perimenopausal body changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women | 22.4 Visual Analogue scale 0-100 mm | Standard Deviation 20.1 |
| Placebo Comparator | Perception of Interference of Perimenopausal Body Changes With Usual Activities in Women | 27.8 Visual Analogue scale 0-100 mm | Standard Deviation 24.2 |
Secondary
Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women
Final perceptions of interference of perimenopausal mood changes with usual activities (as recorded by the CeMCOR Perimenopause Interference Questionnaire \[CeMCOR PIQ\]) in women randomized to the progesterone versus to placebo. Scale Name: Perceived Interference Score: 100 mm line (0 = No Interference; 100 = Severe Interference)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women | 22.7 Visual Analogue scale 0-100 mm | Standard Deviation 20.1 |
| Placebo Comparator | Perception of Interference of Perimenopausal Mood Changes With Usual Activities in Women | 29.3 Visual Analogue scale 0-100 mm | Standard Deviation 23.5 |
Secondary
Sleep Problems
Daily average rating of sleep problems (0-4) from prospective daily calendar records. Outcome is the average daily rating during the final 28 days of therapy, to be analysed with 28-day run-in scores as covariate. Scale name: Sleep Problems (4=Worst, 0=None)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Sleep Problems | 0.8 Units on a ordinal Scale | Standard Deviation 0.8 |
| Placebo Comparator | Sleep Problems | 1.0 Units on a ordinal Scale | Standard Deviation 0.9 |
Secondary
Women's Perceived Changes in Daytime Hot Flushes for Whole Population
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire. Scale Name: Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks). No calculation is needed.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Daytime Hot Flushes for Whole Population | -2.3 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.3 |
| Placebo Comparator | Women's Perceived Changes in Daytime Hot Flushes for Whole Population | -1.8 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.3 |
Secondary
Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire and by subgroup for Early Perimenopause. Scale Name: Perceived Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause | -1.7 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.9 |
| Placebo Comparator | Women's Perceived Changes in Daytime Hot Flushes in Early Perimenopause | -1.3 Change Scale -5 to +5, no change is 0 | Standard Deviation 1.8 |
Secondary
Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Daytime Hot Flushes (both number and severity) as recorded on the Final Questionnaire and by subgroup for Late Perimenopause. Scale Name: Perceived Daytime Hot Flush Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause | -2.5 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.1 |
| Placebo Comparator | Women's Perceived Changes in Daytime Hot Flushes in Late Perimenopause | -2.0 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.4 |
Secondary
Women's Perceived Changes in Night Sweats for Whole Population
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire. Scale Name: Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks). No calculation is needed.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Night Sweats for Whole Population | -2.5 Change Scale -5 to +5, no change is 0 | Standard Deviation 2 |
| Placebo Comparator | Women's Perceived Changes in Night Sweats for Whole Population | -1.9 Change Scale -5 to +5, no change is 0 | Standard Deviation 2 |
Secondary
Women's Perceived Changes in Night Sweats in Early Perimenopause
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire and by subgroup for Early Perimenopause. Scale Name: Perceived Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Night Sweats in Early Perimenopause | -2.9 Change Scale -5 to +5, no change is 0 | Standard Deviation 1.9 |
| Placebo Comparator | Women's Perceived Changes in Night Sweats in Early Perimenopause | -1.9 Change Scale -5 to +5, no change is 0 | Standard Deviation 1.6 |
Secondary
Women's Perceived Changes in Night Sweats in Late Perimenopause
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in Nighttime Night Sweats (both number and severity) as recorded on the Final Questionnaire and by subgroup for Late Perimenopause. Scale Name: Perceived Night Sweats Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Night Sweats in Late Perimenopause | -2.4 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.1 |
| Placebo Comparator | Women's Perceived Changes in Night Sweats in Late Perimenopause | -1.9 Change Scale -5 to +5, no change is 0 | Standard Deviation 2.2 |
Secondary
Women's Perceived Changes in Quality of Sleep for Whole Population
Women's Perceived Changes Questionnaire of changes (from -5 to 0 to +5) in the quality of sleep over the three months of the trial as assessed by the Final Questionnaire based on their random assignment to the progesterone or placebo arms of this RCT (Randomized Controlled Trial) and by Early/Late perimenopause. Scale Name: Quality of Sleep Change Decrease is -5 to -1; No change is 0; Increase is +1 to +5. This is women's perception of the change from run-in to when they recorded it at the end of the trial (at 12 weeks). No calculation is needed.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Oral Micronized Progesterone | Women's Perceived Changes in Quality of Sleep for Whole Population | 2.0 Change Scale -5 to +5, no change is 0 |
| Placebo Comparator | Women's Perceived Changes in Quality of Sleep for Whole Population | 0.0 Change Scale -5 to +5, no change is 0 |